Summary of Work: We have tested the involvement of a ser/thr protein phosphatase, PP5, in the stimulation of BK channel activity by somatostatin through arachidonic acid metabolism in rat pituitary tumor cells (GH4C1) with two molecular reagents: a dominant negative molecule made from the amino terminal regulatory domain containing multiple tetratricopeptide repeats (TPR) of PP5 and the green fluorescent protein; and a toxin-resistant P5 made by a point mutation in the toxin binding site on the catalytic domain of the phosphatase. Stable overexpression of the TPR domain prevents BK channel stimulation by somatostatin in GH4 cells. In contrast, transfection of GH4C1 cells with the mutant, but not the wild type enzyme, rescues somatostatin signaling in the presence of concentrations of okadaic acid in tenfold excess of those which normally block somatostatin action completely. - protein phosphatase, G protein, arachidonic acid, somatostatin